We propose to use the congenitally athymic (nude) mouse for investigations in three general areas of immunology: 1. Nude mice and their normal littermates (NLM) will be used to analyze "thymus- independent" immune responses. The response of nudes and NLM to Vi antigen and group A streptococcal polysaccharide (APS) will be studied. We will examine dose-response relationships, mitogenicity, memory, unresponsiveness and regulation by thymus-derived cells. Using Vi, APS, lipopolysaccharide (LPS) and type III pneumococcal polysaccharide (SSSIII), we will study the regulation by thymus-derived cells of "thymus-independent" immune responses. Similar studies of regulation will utilize antigens which induce homocytotropic IgE antibody. Attempts will be made to alter the "thymus-dependence" or "thymus- independence" of antigens. Nude mice and "thymus-independent" antigens will be used to characterize the stimulated cells and stimulating cells which are active in the allogenic effect. 2. Nude mice and NLM will be used to study the mechanism of the xenograft reaction and to develop model xenograft systems useful in human medicine. Using nude and NLM mice, lymphoid cell transfer and class-specific suppression of immunoglobulin production by heterologous anti-immunoglobulin antisera, we will evaluate the relative roles of immunoglobulins of the various classes in the rejection or protection of xenografts. We will determine if graft alteration occurs while xenografts are maintained on nude mice. Model xenograft systems, using human tissue, will be developed which will be useful in studying, without the direct involvement of human subjects, the mechanism and management of human diseases. 3. The development of autoimmune disorders in conventionally-reared and germfree nude mice will be studied.